Severe gastrointestinal hemorrhage related to everolimus: a case report

Life-Threatening Everolimus-Associated Erosive-Hemorrhagic Gastropathy in a Liver Transplant Patient

“…A) bleeding antral angiodysplasias that were treated with argon plasma coagulation (everolimus 3.5 mg/ daily); B) gastric antral bleeding erosions in a context of hyperemic and fragile mucosa (everolimus 4 mg/daily); C) endoscopic appearance 1 week after everolimus discontinuation. it presented as hemorrhagic colitis, while in the only case reported in a LT patient no definite source of bleeding was identified after repeated lower and upper GI tract endoscopic examinations [6][7][8][9][10] . Our patient presented for the first time, even considering his pre-LT clinical history, with GI bleeding that was initially interpreted as multifactorial: he was on prophylactic antiplatelet therapy with ASA and initially had concomitant endoscopic findings of gastric and colic angiodysplasia, all of them endoscopically apparently non-bleeding in the investigations performed after the first episode of melena and anemia.…”

“…Rare cases of severe hemorrhage have been reported in the literature during treatment with mTOR inhibitors, either everolimus or temsirolimus [6][7][8][9][10][11] . In five cases previously documented in the literature the patients were undergoing chemotherapy (2 cases for breast cancer, 2 cases for renal cancer, 1 case for metastatic neuroendocrine tumor), and in just one report the patient had previously undergone LT [6][7][8][9][10][11] . In four of the 5 cases bleeding originated from the upper digestive tract, and in one case Figure 1.…”

“…The most common adverse effects of everolimus include stomatitis, diarrhea, asthenia, rash, fatigue, vomiting and dry mouth, while gastrointestinal bleeding is not reported among them 4,5 . Very few cases of gastrointestinal (GI) bleeding associated with use of everolimus during chemotherapy consisting in mTOR inhibitors have been documented in the literature, and only one case in a LT patient was reported after two years of everolimus and concomitant introduction of apixaban [6][7][8][9][10] .…”

Hemorrhagic Colitis Caused by Everolimus in a Patient with Nonfunctional Pancreatic Neuroendocrine Neoplasms: A Case Report

“…These reports suggest some relationship between mTOR inhibitors and gastrointestinal bleeding. The mTOR inhibitors may prevent mucosal healing in the stomach and trigger gastrointestinal bleeding [ 8 ].…”

A real-world disproportionality analysis of Everolimus: data mining of the public version of FDA adverse event reporting system

“…Everolimus is already approved for: 1) hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer with exemestane in postmenopausal women ( Du et al, 2018 ; Moreau-Bachelard et al, 2023 ), 2) advanced renal cell carcinoma after treatment with sorafenib or sunitinib therapy ( Yangyun et al, 2022 ), 3) advanced pancreatic neuroendocrine tumors (panNET) ( Chan et al, 2017 ), 4) renal angiomyolipoma or subependymal giant-cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) ( Song et al, 2019 ), and has also been proposed for improving graft function in transplant patients ( Tang et al, 2015 ). While generally well-tolerated with common adverse drug reactions (ADRs) such as stomatitis, anemia, hyperglycemia, and hyperlipidemia ( Paplomata et al, 2013 ), some uncommon but potentially fatal adverse effects warrant specific attention, including non-infectious pneumonitis ( Dabydeen et al, 2012 ) and gastrointestinal hemorrhage ( Tsunematsu et al, 2019 ). Therapeutic drug monitoring adverse events (AEs) should be valued during the use of Everolimus, and more relevant real-world data is necessary for establishing clinically reasonable drug reference standards.…”